Relationship between blood glucose variability and muscle composition in ICU patients receiving nutrition support: A pilot study.

BACKGROUND AND AIMS: Many critically ill patients experience increased blood glucose variability (BGV). The objective of the current pilot study was to assess the relationship between muscle composition (defined as average Hounsfield units (HU)) among ICU patients with an abdominal CT scan within seven days of intubation, and BGV (defined as coefficient of variation (CV)) calculated from blood glucose levels measured each morning while intubated. METHODS: The first serum blood glucose measurement obtained each day during intubation was recorded, blood glucose CV ((mean/SD)∗100) was calculated. Cross-sectional muscle area (CSA; cm2) at the third lumbar region was identified using the -29 to +150 HU range; muscle composition was calculated as the average HU. BGV predictors were determined using linear regression. RESULTS: Eighty-two patients were included (53% female), with a median age of 64 (25th, 75 percentile (IQR): 51, 70) years. The median CV was 29% (IQR: 20, 37); 40% of subjects required insulin. The median CSA was 100.4 cm2 (IQR: 84.0, 120.8) and muscle composition was 20.4 HU (IQR: 12.2, 29.4). Patients received only 36% of estimated calorie requirements. Insulin administration, history of diabetes, and muscle composition were significant BGV predictors. CONCLUSION: Among these adult intubated ICU patients, higher muscle composition was associated with lower BGV. Future research is needed to corroborate these findings, determine other factors associated with poor muscle quality, and identify methods to describe muscle composition for all ICU patients.

Impact of MnSOD and GPx1 Genotype at Different Levels of Enteral Nutrition Exposure on Oxidative Stress and Mortality: A Post hoc Analysis From the FeDOx Trial.

BACKGROUND: Converting nutrition support to energy results in mitochondrial free radical production, possibly increasing oxidative stress. Highly prevalent single nucleotide variants (SNV) exist for the genes encoding antioxidant enzymes responsible for the detoxification of reactive oxygen species. Our objective was to explore the interaction between nutrition support and genetic SNV's for two anti-oxidant proteins (rs4880 SNV for manganese superoxide dismutase and rs1050450 SNV for glutathione peroxidase 1) on oxidative stress and secondarily on intensive care unit (ICU) mortality. METHODS: We performed a post-hoc analysis on 34 mechanically ventilated sepsis patients from a randomized control feeding trial. Participants were dichotomized into those who carried both the rs4880 and the rs1050450 at-risk alleles (Risk Group) versus all others (Nonrisk Group). We explored the interaction between genotype and percent time spent in the upper median of energy exposure on oxidative stress and ICU mortality. RESULTS: Adjusting for confounders, the slope of log F2-isoprostane levels across percentage of days spent in the upper median of daily kilocalories per kilogram (kcal/kg) was 0.01 higher in the Risk Group compared to the Non-Risk Group (p=0.01). Every 1 percent increase in days spent in the upper median of daily kcal/kg was associated with an adjusted 10.3 percent increased odds of ICU mortality amongst participants in the Risk Group (odds ratio [OR]=1.103, p=0.06) but was highly insignificant in the Nonrisk group (OR=0.991, P=0.79). CONCLUSION: Nutrition support may lead to increased oxidative stress and worse clinical outcomes in a large percent of ICU patients with an at-risk genotype.

Real-Time Energy Exposure Is Associated With Increased Oxidative Stress Among Feeding-Tolerant Critically Ill Patients: Results From the FEDOX Trial.

BACKGROUND: Prospective randomized controlled trials (PRCTs) that found harm in patients receiving higher levels of energy exposure have been largely ignored, in part because of the lack of a known mechanism of harm. OBJECTIVE: The current 7-day pilot study is a PRCT and post hoc analysis designed to explore the relationship between energy exposure and oxidative stress (as plasma total F2-isoprostanes) in mechanically ventilated intensive care unit patients with systemic inflammatory response syndrome. METHODS: Thirty-five participants were randomized to receive either 100% or 40% of their estimated energy needs. Our intent-to-treat model found no differences in F2-isoprostanes between groups. A post hoc analysis revealed that on days when participants were in the highest tertile of daily kcal/kg, the real-time energy flow rate within 2 hours of the blood draw was predictive of increased oxidative stress. On these days, participants in the second or third vs the first tertile of real-time energy flow rate experienced a 41.8% (P = .006) or 26.5% (P = .001) increase in F2-isoprostane levels, respectively. This was confirmed through a within-group subanalysis restricted to participants with measurements on both sides of the median of real-time energy flow rate that found a 28.2% F2-isoprostane increase on days in the upper vs lower median of flow rate (P = .002). CONCLUSION: The benefits of feeding may be more nuanced than previously suspected. Our findings imply a potential mechanism of harm in meeting the current recommendations for nutrition support in the critically ill that warrants further investigation.

American Society for Parenteral and Enteral Nutrition Clinical Guidelines: The Validity of Body Composition Assessment in Clinical Populations.

On behalf of the American Society for Parenteral and Enteral Nutrition (ASPEN), a systematic review was conducted to evaluate the best available evidence regarding the validity of relevant body composition methods (eg, dual energy X-ray absorptiometry [DXA], ultrasound [US], and bioelectrical impedance analysis [BIA]) in clinical populations. The guidelines targeted adults >18 years of age with a potentially inflammatory condition or pathological end point associated with a specific disease or clinical condition. In total, 7375 studies were retrieved, and 15 DXA, 7 US, and 23 BIA studies provided applicable data. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to assess the diagnostic accuracy of the test method against a "gold standard" reference. The Grading of Recommendations, Assessment, Development and Evaluation criteria were used to separate the evaluation of the body of evidence from the recommendations. Based on a limited number of studies and expert opinion, DXA is recommended for the assessment of fat mass in patients with a variety of disease states; however, the validity of DXA for lean mass assessment in any clinical population remains unknown. No recommendations can be made at this time to support the use of US or BIA in the clinical setting, as data to support its validity in any specific patient population are limited in scope or by the proprietary nature of manufacture-specific BIA regression models to procure body composition data, respectively. Directions for future research are provided. These clinical guidelines were approved by the ASPEN Board of Directors.

Higher Caloric Exposure in Critically Ill Patients Transiently Accelerates Thyroid Hormone Activation.

INTRODUCTION: The inflammatory response of critical illness is accompanied by nonthyroidal illness syndrome (NTIS). Feeding has been shown to attenuate this process, but this has not been explored prospectively over time in critically ill patients. OBJECTIVE: To explore the impact of calorie exposure on NTIS over time in critically ill patients. METHODS: Mechanically ventilated patients with systemic inflammatory response syndrome (SIRS) were randomized to receive either 100% or 40% of their estimated caloric needs (ECN). Thyroid hormones were measured daily for 7 days or until intensive care unit discharge or death. Mixed level regression modeling was used to explore the effect of randomization group on plasma triiodothyronine (T3), reverse triiodothyronine (rT3), thyroxine (T4), and thyroid stimulating hormone (TSH), as well as the T3/rT3 ratio. RESULTS: Thirty-five participants (n=19 in 100% ECN; n=16 in 40% ECN) were recruited. Adjusting for group differences in baseline T3/rT3 ratio, the parameters defining the fitted curves (intercept, linear effect of study day, and quadratic effect of study day) differed by randomization group (P = 0.001, P = 0.01, and P = 0.02 respectively). Plots of the fitted curves revealed that participants in the 100% ECN group had a 54% higher T3/rT3 ratio on postintervention day 1 compared with the 40% ECN group, a difference which attenuated over time. This was driven by a 23% higher plasma T3 and 10% lower plasma rT3 levels on postintervention 1. CONCLUSIONS: Higher caloric exposure in NTIS patients transiently attenuates the drop of the plasma T3/rT3 ratio, an effect that is minimized and finally lost over the following 3 days of continued higher caloric exposure.

Author Response to "Unraveling Methodology to Ensure the Search for Optimal Nutrition Quantity in Acute Respiratory Distress Syndrome Remains INTACT".

We thank Drs. Patel, Martindale, and Heyland1 for their interest in our most recent study2 exploring the role of early exposure to recommended energy delivery in critically ill patients with acute respiratory distress syndrome. Their stated concerns center around 3 major areas: (1) the comparability of the population in our study2 with those of INTACT (Intensive Nutrition in Acute Lung Injury: A Clinical Trial); (2) their confusion on the analysis of the relationship between the likelihood of death with energy exposure (table 1 in our article2 ); and (3) their apparent misunderstanding of type I error, type II error, P-values, and power analysis. Our responses to each of these areas are detailed as follows.

Combination of High-Calorie Delivery and Organ Failure Increases Mortality Among Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: Among critically ill patients, the benefits of nutrition support may vary depending on severity of organ dysfunction. The objective of the current article was to explore the relationship between organ failure and calories exposure with hospital mortality during the first week of acute respiratory distress syndrome. DESIGN: Retrospective observational study. SETTING: Single-center ICU. PATIENTS: Adults admitted to the ICU with a diagnosis of acute respiratory distress syndrome. INTERVENTIONS: Calorie delivery from enteral nutrition, parenteral nutrition, propofol, and dextrose containing fluids were collected for 7 days following intubation. Sequential Organ Failure Assessment score was calculated at ICU admit and for the same 7 days to describe organ dysfunction; four different Sequential Organ Failure Assessment variables were created 1) Sequential Organ Failure Assessment at ICU admit, 2) average Sequential Organ Failure Assessment for the first 7 days following intubation, 3) the highest Sequential Organ Failure Assessment for the first 7 days following intubation, and 4) change in Sequential Organ Failure Assessment from intubation to 7 days later. MEASUREMENTS AND MAIN RESULTS: A total of 298 patients were included. Sequential Organ Failure Assessment at ICU admit, average Sequential Organ Failure Assessment for the first 7 days following intubation, highest Sequential Organ Failure Assessment for the first 7 days following intubation, change in Sequential Organ Failure Assessment from intubation to 7 days later, and calorie delivery the first 7 days following intubation were all associated with increased likelihood of mortality. Compared with patients with low organ failure and low-calorie delivery, those with high-calorie delivery and low organ failure, low-calorie delivery and high organ failure, and the combination of both high organ failure with high-calorie delivery were associated with an incremental increase in the likelihood or mortality. CONCLUSIONS: Organ failure appears to modify the relationship between calorie exposure and ICU outcome. Additional research is needed to identify appropriate thresholds for safe calorie exposure with increased organ failure.

Early Exposure to Recommended Calorie Delivery in the Intensive Care Unit Is Associated With Increased Mortality in Patients With Acute Respiratory Distress Syndrome.

BACKGROUND: The Intensive Nutrition in Acute Lung Injury: Clinical Trial (INTACT), designed to evaluate outcomes of calorie delivery from acute respiratory distress syndrome (ARDS) diagnosis through hospital discharge, was stopped due to higher mortality in the intervention group. Post hoc analysis found timing and dose of calorie delivery influenced mortality. The objective of this retrospective cohort study was to determine if early vs late calorie exposure changed the hazard of death among a larger sample of patients with ARDS. METHODS: Adult patients who met the eligibility criteria for INTACT but did not participate were included. Daily calorie delivery was collected from the date INTACT eligibility was determined to extubation or death. Cox proportional hazards regression was used to model the relationship between hazard of hospital death with average calorie exposure received over increasing study days and after day 7. RESULTS: A total of 298 patients were included; overall mortality was 33%. Among patients who remained intubated at 1 week (n = 202), higher kcal/kg received from intensive care unit (ICU) days 1-6 increased hazards of subsequent death on days 7+ (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.06); kcal/kg received after ICU day 7 decreased the hazards of death on day 7+ (HR, 0.53; 95% CI, 0.33-0.84). CONCLUSIONS: Higher calorie exposure between ICU days 1 and 7 was associated with higher subsequent hazard of mortality, and provision of high-calorie exposure after day 8 decreased the hazards of death.

Impact of Abdominal Adipose Depots and Race on Risk for Colorectal Cancer: A Case-Control Study.

Visceral adipose tissue (VAT) but not subcutaneous adipose tissue (SAT) is associated with obesity-related diseases including colorectal cancer (CRC). Superficial SAT (SSAT) and deep SAT (DSAT), components of SAT, also appear to independently influence disease risk. These abdominal adipose tissues (AATs) are not extensively studied in connection with CRC and have not been explored in the United States despite known racial variations in body composition. We conducted a case-control study that compared associations between AAT with CRC risk and race of African-American (AA) and non-Hispanic white (NHW) men with incident CRC matched by age, body mass index, and race (N = 158, 79/group). Cross-sectional computed tomography images were used for assessment of AAT. Overall cases and controls had similar VAT areas (140 ± 192 vs 149 ± 152 cm2, P-value = 0.93); however, cases had lower SSAT than controls (88 ± 39 vs 112 ± 65 cm2, P < 0.01). Among controls, AA had significantly lower VAT (114 ± 168 vs 180 ± 167, P < 0.01) than NHW. Conditional logistic regression revealed that AA men with greater SSAT had lower odds for CRC (odds ratio [OR]: 0.24, 95% confidence interval [CI] 0.07-0.85). Our findings indicate that VAT does vary between cases and controls by race; however, this variation is not a risk factor for CRC. The negative association between CRC and SSAT in AA men warrants further investigation.

Economic Burden of Disease-Associated Malnutrition at the State Level.

BACKGROUND: Disease-associated malnutrition has been identified as a prevalent condition, particularly for the elderly, which has often been overlooked in the U.S. healthcare system. The state-level burden of community-based disease-associated malnutrition is unknown and there have been limited efforts by state policy makers to identify, quantify, and address malnutrition. The objective of this study was to examine and quantify the state-level economic burden of disease-associated malnutrition. METHODS: Direct medical costs of disease-associated malnutrition were calculated for 8 diseases: Stroke, Chronic Obstructive Pulmonary Disease, Coronary Heart Failure, Breast Cancer, Dementia, Musculoskeletal Disorders, Depression, and Colorectal Cancer. National disease and malnutrition prevalence rates were estimated for subgroups defined by age, race, and sex using the National Health and Nutrition Examination Survey and the National Health Interview Survey. State prevalence of disease-associated malnutrition was estimated by combining national prevalence estimates with states' demographic data from the U.S. Census. Direct medical cost for each state was estimated as the increased expenditures incurred as a result of malnutrition. PRINCIPAL FINDINGS: Direct medical costs attributable to disease-associated malnutrition vary among states from an annual cost of $36 per capita in Utah to $65 per capita in Washington, D.C. Nationally the annual cost of disease-associated malnutrition is over $15.5 billion. The elderly bear a disproportionate share of this cost on both the state and national level. CONCLUSIONS: Additional action is needed to reduce the economic impact of disease-associated malnutrition, particularly at the state level. Nutrition may be a cost-effective way to help address high health care costs.

Prevalence of Sarcopenia and Associated Outcomes in the Clinical Setting.

Sarcopenia refers to age-associated decrease in muscle mass and function. The condition was originally described in the elderly, but emerging evidence suggests that it is also a concern among the chronically ill nonelderly. Currently there are a number of definitions for diagnosing sarcopenia; however, in the clinical setting, abdominal computed tomography (CT) scans completed for diagnostic purposes can be utilized to identify CT-defined sarcopenia. Recent studies suggest that prevalence of CT-defined sarcopenia is high among chronically ill patients, ranging from 15%-50% in patients with cancer, 30%-45% with liver failure, and 60%-70% for critically ill patients in the intensive care unit. Depleted muscle mass is associated with infectious complications, prolonged duration of mechanical ventilation, longer hospitalization, greater need for rehabilitation care after hospital discharge, and higher mortality. In consideration of the growing population of older adults with multiple comorbidities, more research is needed to identify sarcopenia and develop interventions that are directed at attenuating or reversal muscle loss.

Intensive nutrition in acute lung injury: a clinical trial (INTACT).

BACKGROUND: Despite extensive use of enteral (EN) and parenteral nutrition (PN) in intensive care unit (ICU) populations for 4 decades, evidence to support their efficacy is extremely limited. METHODS: A prospective randomized trial was conducted evaluate the impact on outcomes of intensive medical nutrition therapy (IMNT; provision of >75% of estimated energy and protein needs per day via EN and adequate oral diet) from diagnosis of acute lung injury (ALI) to hospital discharge compared with standard nutrition support care (SNSC; standard EN and ad lib feeding). The primary outcome was infections; secondary outcomes included number of days on mechanical ventilation, in the ICU, and in the hospital and mortality. RESULTS: Overall, 78 patients (40 IMNT and 38 SNSC) were recruited. No significant differences between groups for age, body mass index, disease severity, white blood cell count, glucose, C-reactive protein, energy or protein needs occurred. The IMNT group received significantly higher percentage of estimated energy (84.7% vs 55.4%, P < .0001) and protein needs (76.1 vs 54.4%, P < .0001) per day compared with SNSC. No differences occurred in length of mechanical ventilation, hospital or ICU stay, or infections. The trial was stopped early because of significantly greater hospital mortality in IMNT vs SNSC (40% vs 16%, P = .02). Cox proportional hazards models indicated the hazard of death in the IMNT group was 5.67 times higher (P = .001) than in the SNSC group. CONCLUSIONS: Provision of IMNT from ALI diagnosis to hospital discharge increases mortality.

The prevalence of sarcopenia in patients with respiratory failure classified as normally nourished using computed tomography and subjective global assessment.

BACKGROUND: Declines in nutrition status and adverse body composition changes frequently occur in the critically ill. The objective of this cross-sectional study was to examine the prevalence of sarcopenia and its occurrence in patients classified as normal nourished using subjective global assessment (SGA). METHODS: Exploiting diagnostic CT images, skeletal muscle mass at the L3 region was quantified and used to determine sarcopenia and its association with normal nutrition status in 56 patients with respiratory failure. Sarcopenia was defined as an L3 skeletal muscle index of ≤38.5 cm(2)/m(2) for women and ≤52.4 cm(2)/m(2) for men. CT imaging and SGA classifications completed within 14, 10 and 7 days of each other were analyzed to assess sarcopenia and the influence of time between scans on misclassification (ie, normal nourished and sarcopenic). Descriptive statistics were conducted. RESULTS: The average patient was 59.2 (± 15.6) years old, admitted with sepsis/infection, an APACHE II score of 26 (± 8.0), and BMI of 28.3 (± 5.8). Sarcopenia and sarcopenic obesity were prevalent in a minimum of 56% and 24% of patients, respectively, depending on the number of days between CT imaging and SGA assessment. Misclassified individuals were predominantly male, minority and overweight or obese. Controlling for age, no significant differences were noted for patients classified as normal nourished vs malnourished by SGA for lumbar muscle cross-sectional, whole-body lean mass, or skeletal muscle index. CONCLUSIONS: Sarcopenia is highly prevalent among patients with respiratory failure requiring mechanical ventilation (MV) and not readily detected in patients classified as normal nourished using SGA.

Exploitation of diagnostic computed tomography scans to assess the impact of nutrition support on body composition changes in respiratory failure patients.

BACKGROUND: Assessment of nutritional status in intensive care unit (ICU) patients is limited. Computed tomography (CT) scans that include the first to fifth lumbar region completed for diagnostic purposes measures fat and lean body mass (LBM) depots and are frequently done in ICU populations and can be used to quantify fat and LBM depots. The purpose of this study was to assess if these scans could measure change in skeletal muscle (SKT), visceral adipose (VAT), and intermuscular adipose (IMAT) tissue and to examine the association between the amount of energy and protein received and changes in these depots. METHODS: Cross-sectional area of SKT, VAT, and IMAT from CT scans at the third lumbar region was quantified at 2 time points (CT1 and CT2). Change scores between CT1 and CT2 for each of these depots and the percentage of estimated energy/protein needs received were determined in 33 adults that with acute respiratory failure. Descriptive statistics and multiple regression was used to evaluate the influence of baseline characteristics and the percentage energy/protein needs received between CT1 and CT2 on percentage change/day between CT1 and CT2 on SKM, IMAT, and VAT. RESULTS: Participants were on average (SD) 59.7 (16) years old, received 41% of energy and 57% of protein needs. The average time between CT1 and CT2 was 10 (5) days. SKM declined 0.49%/day (men P = .07, women P = .09) and percentage of energy needs received reduced loss (ß = 0.024, P = .03). No change in VAT or IMAT occurred. CONCLUSIONS: CT scans can be exploited to assess change in body composition in ICU patients and may assist in detecting the causal link between nutritional support and outcomes in future clinical trials.

Utilizing multiple methods to classify malnutrition among elderly patients admitted to the medical and surgical intensive care units (ICU).

BACKGROUND & AIMS: The nutritional status of elderly patients requiring ICU admission is largely unknown. This study evaluated the prevalence of malnutrition in elderly patients (>65 years) admitted to the surgical and medical ICUs, agreement between assessment techniques and associations between malnutrition and adverse outcomes. METHODS: For this prospective cohort, nutritional status was classified concurrently using the Mini Nutrition Assessment (MNA), Subjective Global Assessment (SGA), Nutrition Risk Score 2002 (NRS 2002) and MNA-short form (MNA-SF). Demographic and relevant medical information were collected from the medical record prior to the nutrition interview and/or following hospital discharge. Descriptive statistics, inter-rater agreement and regression analyses were conducted. RESULTS: The average patient was 74.2 (±6.8) years of age with a mean APACHE II score of 11.9 (±3.6). Malnutrition was prevalent in 23-34% of patients (n = 260) with excellent agreement between raters. Compared to MNA, NRS 2002 had the highest sensitivity, while SGA and MNA-SF had higher specificity. Malnutrition at ICU admission was associated with longer hospital LOS, a lower propensity for being discharged home and a greater need for hospice care or death at discharge (all p values <0.05). These relationships were diminished when controlling for severity of illness. CONCLUSIONS: Future work in this elderly population needs to explore the role of disease acuity, inflammation and body composition in the nutrition assessment process and in the examination of outcomes.

Intensive medical nutrition therapy: methods to improve nutrition provision in the critical care setting.

Patients requiring mechanical ventilation in an intensive care unit commonly fail to attain enteral nutrition (EN) infusion goals. We conducted a cohort study to quantify and compare the percentage of energy and protein received between standard care (n=24) and intensive medical nutrition therapy (MNT) (n=25) participants; to assess the percentage of energy and protein received varied by nutritional status, and to identify barriers to EN provision. Intensive MNT entailed providing energy at 150% of estimated needs, using only 2.0 kcal/cc enteral formula and 24-hour infusions. Estimated energy and protein needs were calculated using 30 kcal/kg and 1.2 g protein/kg actual or obesity-adjusted admission body weight. Subjective global assessment was completed to ascertain admission intensive care unit nutritional status. Descriptive statistics and survival analyses were conducted to examine time until attaining 100% of feeding targets. Patients had similar estimated energy and protein needs, and 51% were admitted with both respiratory failure and classified as normally nourished (n=25/49). Intensive MNT recipients achieved a greater percentage of daily estimated energy and protein needs than standard care recipients (1,198±493 vs 475±480 kcal, respectively, P<0.0001; and 53±25 vs 29±32 g, respectively, P=0.007) despite longer intensive care unit stays. Cox proportional hazards models showed that intensive MNT patients were 6.5 (95% confidence interval 2.1 to 29.0) and 3.6 (95% confidence interval 1.2 to 15.9) times more likely to achieve 100% of estimated energy and protein needs, respectively, controlling for confounders. Malnourished patients (n=13) received significantly less energy (P=0.003) and protein (P=0.004) compared with normally nourished (n=11) patients receiving standard care. Nutritional status did not affect feeding intakes in the intensive MNT group. Clinical management, lack of physician orders, and gastrointestinal issues involving ileus, gastrointestinal hemorrhage, and EN delivery were the most frequent clinical impediments to EN provision. It was concluded that intensive MNT could achieve higher volumes of EN infusion, regardless of nutritional status. Future studies are needed to advance this methodology and to assess its influence on outcomes.